ANTIBODIES TO DEIMINATED HUMAN FIBRINOGEN (ADF) ARE HIGHLY SPECIFIC FOR RHEUMATOID ARTHRITIS

Background: Antibodies to deiminated peptides or proteins were shown to be very specifically present in serum of patients with rheumatoid arthritis (RA). Recently, it has been demonstrated that deiminated fibrin can be detected in synovial tissue from RA patients. Consequently, deiminated fibrinogen was proposed to be a physiological substrate to assay antibodies recognizing deiminated structures. To measure those antibodies an ELISA was developed.Objectives: To assess the value of antibodies to deiminated human fibrinogen (ADF) for diagnosing RA and compare the results with IgM-RF and the commercially available, second generation anti-cyclic citrullinated peptide (anti-CCP) assay.Methods: Antibodies to deiminated fibrinogen were detected by an ELISA using IgG depleted, in vitro deiminated human fibrinogen, purified from plasma. A highly positive patient serum was used as internal standard and tested in 8 dilutions with each plate. The anti-CCP ELISA was performed according to the manufacturer's recommendations and the IgM-RF was measured using an in-house ELISA. ADF, anti-CCP and IgM-RF were measured in 421 sera (53 clinically active RA patients, 186 RA patients in clinical remission, 91 patients without arthritis and 91 healthy controls). Of the three tests, the area under the receiver operating characteristic (ROC) curve was calculated and the sensitivities were compared at three specificities (95%, 98.5% and 99%).Results: At a high specificity of 99%, the sensitivity of the ADF test and the anti-CCP test was 67.8% and 71.1%, respectively. At this specificity, the IgM-RF test had a sensitivity of only 41.8%. The area under the ROC-curve of the ADF test and the anti-CCP test were 0.893 and 0.903, respectively. The area under the ROC-curve of the IgM-RF test was significantly smaller than that of the ADF-test and the anti-CCP test (table). Sensitivity and specificity of IgM-RF, anti-CCP and ADF Test 95% Specificity 99% Area under Confidence 98.5% ROC-curve interval IgM-RF 49.8% 45.2% 41.8% 0.726 0.678 - 0.774 anti-CCP 72.0% 71.1% 71.1% 0.903 0.873 - 0.932* ADF 72.4% 67.8% 67.8% 0.893 0.861 - 0.925* * statistically significant in comparison with IgM-RF tatistically significant in comparison with IgM-RFConclusion: The ADF-test is a very specific test for RA. At high specificities, the ADF-test is as sensitive as the second generation anti-CCP test and more sensitive than the IgM-RF test.Citation: , volume , supplement , year 2003, page Session: Rheumatoid arthritis – Clinical aspects